Current trends of human population growth and landscape development show that human-wildlife conflicts are increasing worldwide (e.g. Rutberg, A. T. and Naugle, R. E. (2008) Population effects of immunocontraception in white-tailed deer (Odocoileus virginianus) Wildlife Research 35, 494-501; White P. C. L., and Ward A. I. (2010) Interdisciplinary approaches for the management of existing and emerging human-wildlife conflicts Wildlife Research 37, 623-629; and Gionfriddo J. P., Denicol, A. J., Miller L. A., and Fagerstone K. A. (2011) Efficacy of GnRH immunocontraception of wild white-tailed deer in New Jersey. Wildlife Society Bulletin 35, 142-148). As human populations expand and economies grow, the scale of these conflicts increase and new threats emerge, particularly with respect to biodiversity and zoonotic disease. There is thus a need to develop humane, economically viable and environmentally sustainable methods to resolve these conflicts. Only recently fertility control technologies (FCT) have begun to emerge that offer potential for contributing to human-wildlife conflict resolution. In particular, immunocontraception, using a vaccine to generate an immune response to some key component of the target's reproductive system, has moved from theory into practice with the development of “single-shot” injectable vaccines (Miller L. A., Johns B. E. and Killian G. J. (2000) Immunocontraception of white-tailed deer with GnRH vaccine American Journal of Reproductive Immunology 44, 266-274; Curtis P. D., Pooler R. L., Richmond M. E., Miller L. A., Mattfeld G. F., and Quimby F. W. (2002) Comparative effects of GnRH and porcine zona pellucida (PZP) immunocontraceptive vaccines for controlling reproduction in white-tailed deer (Odocoileus virginianus) Reproduction 60, 131-141).
The cell wall of Mycobacterium is unique among bacteria, being comprised of a plasma membrane underlying a complex matrix of carbohydrates and lipids, surrounded by an outer “capsule” comprised of polysaccharides and protein. Exact components vary by species, but elements of the mycobacterial cell wall are highly immunogenic in mammals, activating a large array of immune-related cellular receptors on several immune cell types (Britton and Triccas, 2008). Whole, killed bacteria of the genus Mycobacterium have long been included in injectable vaccine formulations as an adjuvant. Freunds Complete Adjuvant, comprised of a water/mineral oil emulsion and killed, dried Mycobacterium sp. (usually M. tuberculosis) has been referred to as the “gold standard for many years” (Colavecchia et al. 2012).
However, development of commercial oral vaccines is challenging as demonstrated by the fact that out of many hundreds of vaccines, only a few orally administered vaccines currently exist e.g. cholera, polio, rabies and BCG. Typically, live particulate forms appear to be most successful in producing an immune response. Oral delivery requires 10-100 fold more antigen in the best of conditions to produce an adequate immune response compared to parenteral delivery. Furthermore, successful oral vaccines have been disease related where there is a potential boost of antibody, resulting in extended protection, in response to disease challenge. This “simulated disease” may have to be a delayed oral boost. A successful oral immunocontraceptive vaccine will need to be economical to produce, it must be protected from the acid and enzymes of the gut and must pass through the mucus layer over the epithelial cells. Against this challenging background research has been carried out into developing orally active immunocontraceptive vaccines. Oral formulations of commercially available injectable immunocontraceptive vaccines have failed to provide contraceptive effects in rabbits and domestic pigs.
Further, whole Mycobacteria, even when killed, tend to form clumps which render the cell wall surfaces on the clumps' interior unavailable for chemical manipulation. Thus, there is a need for a product which can improve on the currently-known whole, killed Mycobacteria to stimulate an immune response, and further to create a product which can be administered orally.
All of the references cited herein, including U.S. patents and U.S. Patent Application Publications, are incorporated by reference in their entirety.